Table 1.

Reciprocal relationship between PI3K/AKT signaling pathway and ncRNAs in DM and its related complications.

Non-coding RNAs	Name	Expression levels	Interaction with target molecules	Associated complication	Study samples	Effect on PI3K/Akt pathways	Refs.
MiRNAs	miR-27a	Upregulated	Directly target PPAR-γ	–	mouse model/3T3-L1	Inhibit PI3K/Akt pathways	[54]
	miR-351	Downregulated	Directly target FLOT2	GDM	GDM mice	Inhibit PI3K/Akt pathways	[56]
	miR-26b	Upregulated	Indirectly target PI3K/Akt signaling pathway	GDM	GDM mice	Inhibit PI3K/Akt pathways	[103]
	miR-125a-5p	Downregulated	Directly target STAT3	–	C57BL/6 mice	Activate PI3K/Akt pathways	[60]
	miR-21	Upregulated	Directly target PTEN	DR	DR models/RVECs	Activate PI3K/Akt pathways	[61]
		Downregulated	Indirectly regulated by PI3K/Akt	–	C57BL/6/Islet cell	PI3K/Akt pathways induce miR-21	[62]
	miR-130b	Downregulated	Directly target PTEN	DE	PC12/hippocampal cells/Male Wistar rats	Activate PI3K/Akt pathways	[64]
	miR-195	Upregulated	Directly target Mfn2	–	C57BL/6J mice/palmitate-stimulated Min6 cells	Inhibit PI3K/Akt pathways	[65]
		Upregulated	Directly target PFKFB4	–	HCC cell lines/HCC tumor	Inhibit PI3K/Akt pathways	[104]
	miR-7	Downregulated	Directly target HOXB3	DR	ARPE-19 cell line	Inhibit PI3K/Akt pathways	[67]
		Downregulated	Directly target IRS-1	DR	diabetic rat model/ECs and RPs cells	Inhibit PI3K/Akt pathways	[68]
		Downregulated	Directly target IRS-2	DR	mice model of DR/ECs and RPs cells	Inhibit PI3K/Akt pathways	[105]
	miR-363-3p	Downregulated	Indirectly target FOXO1	insulin resistance	C57BL/6J mice/HepG2 cells	Activate PI3K/Akt pathways	[106]
	miR-19a	Upregulated	Directly target PTEN	DR	DR rat model	Inhibit PI3K/Akt pathways	[71]
	miR-122	Upregulated	Indirectly target PI3K/Akt	–	INS-1	Inhibit PI3K/Akt pathways	[107]
	miR-20b-5p	Upregulated	Directly target THBS1	DR	DR model	Inhibit PI3K/Akt pathways	[108]
	miR-30c	Downregulated	Directly target ROCK2	DN	Human DN tissue/HK-2 cells	Inhibit PI3K/Akt pathways	[74]
	miR-199a-3p	Downregulated	Directly target FGF7	DR	DR rat model//ECs and RPs cells	Inhibit PI3K/Akt pathways	[75]
		Downregulated	Directly target VEGF	DR	hRMECs and ARPE-19 cell	Inhibit PI3K/Akt pathways	[76]
		Downregulated	Indirectly target PI3K/Akt	–	Peripheral blood samples/HUVECs	Activate PI3K/Akt pathways	[77]
	miR-720	Upregulated	Directly target Rab35	–	MIN6 cells/	Activate PI3K/Akt pathways	[78]
	miR-139-5p	Upregulated	Directly target PICK1	–	Min6 cells/db/db mice	Inhibit PI3K/Akt pathways	[79]
	miR-24	Downregulated	Indirectly target PI3K/Akt	CAD	diabetic rats/VSMCs	Inhibit PI3K/Akt pathways	[80]
	miR-183	Upregulated	Directly target BTG1	DR	DR rat model	Activate PI3K/Akt pathways	[81]
	miR-203	Downregulated	Directly target PIK3CA	DCM	DCM mouse model	Inhibit PI3K/Akt pathways	[82]
	miR-153	Downregulated	Directly target PAQR3	DN	MCs/renal tissue from DN	Inhibit PI3K/Akt pathways	[84]
	miR-23b	Downregulated	Directly target HMGA2	DN	db/db mice/HK-2 cells	Inhibit PI3K/Akt pathways	[85]
	miR-126	Downregulated	Directly target IRS1	DR	DR rat model/ECs and RPs cells	Inhibit PI3K/Akt pathways	[86]
		Downregulated	Indirectly target PI3K/Akt	–	Min6 cells	Activate PI3K/Akt pathways	[87]
		Downregulated	Directly target VEGFA, and PK3R2	DR	RF/6A cells	Inhibit PI3K/Akt pathways	[88]
	miR-499-5p	Downregulated	Directly target PTEN	insulin resistance	db/db mice/NCTC1469 cells	Activate PI3K/Akt pathways	[90]
	miR-873	Upregulated	Directly target IGFBP2	myocardial injury/insulin resistance	GDM rat model	Inhibit PI3K/Akt pathways	[91]
lncRNAs	MEG3	Downregulated	Indirectly target PI3K/Akt	DR	DR Rat Models/Microvascular endothelial cells from rat retina	Inhibit PI3K/Akt pathways	[92]
		Upregulated	Directly target miR-370-3p	GDM	HUVEC cell	Inhibit PI3K/Akt pathways	[109]
	PVT1	Downregulated	Indirectly target PI3K/Akt	DPN	DPN Rat Models	Activate PI3K/Akt pathways	[110]
		Upregulated	Indirectly target PI3K/Akt	GDM	HTR-8/SVneo cell/trophoblast cells	Activate PI3K/Akt pathways	[95]
	SNHG16	Upregulated	Directly target miR-146a, and miR-7-5p	DR	hRMECs	Activate PI3K/Akt pathways	[96]
	RPL13p5	Upregulated	Indirectly target PI3K/Akt	GDM	peripheral blood	Activate PI3K/Akt pathways	[111]
	UCA1	Upregulated	Indirectly target PI3K/Akt	DN	DN rat model	Activate PI3K/Akt pathways	[112]
	HOTAIR	Downregulated	Indirectly target PI3K/Akt	DCM	Myocardial biopsy/AC16 cell	Activate PI3K/Akt pathways	[99]
	TUG1	Downregulated	Indirectly target PI3K/Akt	DN	DM rats/Mouse-derived mesangial cells	Inhibit PI3K/Akt pathways	[113]
	LINC00323	Upregulated	Indirectly target PI3K/Akt	DN	blood samples of DN patients	Activate PI3K/Akt pathways	[101]
	HEIH	Upregulated	Directly target miR-939	DR	ARPE-19/DR patients	Activate PI3K/Akt pathways	[102]